RESUMO
Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34-0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53-6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.
Assuntos
Anemia Falciforme/genética , Anemia Falciforme/microbiologia , Infecções Bacterianas/genética , Receptor 2 Toll-Like/genética , Adolescente , Adulto , África/epidemiologia , Idoso , Anemia Falciforme/epidemiologia , Anemia Falciforme/imunologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/imunologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Haemoglobin (Hb) SC disease is the second most common subtype of sickle cell disease and is potentially fatal. This study aimed to determine the clinical characteristics, outcome and predictors of mortality in HbSC disease patients, and to compare these findings with patients followed-up in different centres. Clinical, laboratory and outcome data were collected from a cohort of adult patients with HbSC disease followed between 1991 and 2103. Cox regression multivariate analysis was used to determine predictors of mortality. One hundred and fifty-five patients were followed-up over 20 years: 9% died and 70·8% had at least one complication. The most common complications were: painful crises (38·3%), retinopathy (33·8%), cholelithiasis (30·3%), osteonecrosis (24·8%) and sensorineural hearing disorders (9·7%). Frequency of chronic complications was similar in most studies. In multivariate analysis, hearing disorders remained an independent predictor of mortality (Odds Ratio 9·26, 95% confidence interval 1·1-74·8; P = 0·03). It was concluded that patients with HbSC disease receive a late diagnosis and there is remarkable similarity between the studies conducted in different centres around the world. Sensorineural hearing disorders were an independent predictor of mortality, suggesting that it may be useful to implement routine diagnostic screening.
Assuntos
Doença da Hemoglobina SC/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Colelitíase/etiologia , Comorbidade , Diagnóstico Tardio , Feminino , Seguimentos , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/mortalidade , Doença da Hemoglobina SC/sangue , Doença da Hemoglobina SC/complicações , Doença da Hemoglobina SC/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Dor/etiologia , Gravidez , Complicações Hematológicas na Gravidez/epidemiologia , Modelos de Riscos Proporcionais , Doenças Retinianas/etiologia , Adulto JovemRESUMO
O pulmão é um dos principais alvos de complicações agudas e crônicas nas doenças falciformes (DF). A síndrome torácica aguda é a segunda causa de internação hospitalar apresentando considerável morbimortalidade. O suporte clínico de alta qualidade é a base do tratamento bem sucedido. A administração adequada de fluidos, a analgesia, a oxigenioterapia, a fisioterapia respiratória ativa e o uso criterioso de transfusões sanguíneas são elementos essenciais do tratamento. A hipertensão pulmonar (HP), por sua vez, tem sido recentemente reconhecida como uma das complicações mais graves e freqüentes destes pacientes. A pressão de artéria pulmonar deve ser medida periodicamente por meio de ecocardiografia. Se o diagnóstico de HP for confirmado, o uso de hidroxiuréia, anticoagulação, transfusões e oxigênio deveriam ser considerados. As manifestações cardíacas nas DF incluem cardiomegalia, isquemia miocárdica, disfunção ventricular e cor pulmonale. O tratamento destas complicações deve seguir as recomendações das diretrizes atuais.
The lung is a major target organ for acute and chronic complications in sickle cell disease. Acute chest syndrome is the second most common cause of hospital admission resulting in considerable morbidity and mortality. The mainstay of successful treatment remains high quality supportive care. Fluid management, analgesia, oxygenation, bronchodilators, incentive spirometry and judicious use of transfusion therapy are essential elements of supportive care management. Pulmonary hypertension (PHT) has emerged as one of the most frequent and serious complications in these patients. The pulmonary artery pressure should be evaluated periodically by echocardiography. If the PHT diagnosis is positive the use of hydroxiurea, anticoagulation, transfusions and oxygen therapy should be considered. Cardiac manifestations are common including enlargement of the heart, myocardial ischaemia, ventricular dysfunction and cor pulmonale. The management of these complications follows the current guidelines.
Assuntos
Humanos , Anemia Falciforme , Doença da Hemoglobina SC , Hipertensão Pulmonar , Síndrome Coronariana Aguda/complicaçõesRESUMO
Imatinib mesylate is a specific inhibitor of protein tyrosine kinase activity secondary to bcr-abl, mostly indicated for the treatment of patients with Philadelphia chromosome positive chronic myeloid leukaemia (CML). Generally, the undesirable effects of imatinib administration observed in clinical trials were of mild-to-moderate degree, and no haemolysis has been associated with this drug. We report here a case of immune-mediated haemolytic anaemia associated to imatinib mesylate successfully treated with prednisone in a patient with CML. Laboratory investigation showed anaemia [haemoglobin (Hb) of 59 g/L], reticulocyte of 61 x 10(9)/L and a positive direct antiglobulin test. Anti-drug in vitro studies revealed a positive result with gel microcolumn assay by an adsorption mechanism. Seventy-four days after prednisone therapy, the patient's Hb level was of 110 g/L with negative direct antiglobulin test and drug in vitro studies. This case demonstrated that patients treated with imatinib mesylate can present immune-mediated haemolysis and adequate management of this event can be done maintaining the drug and associating corticosteroids.